We propose jointly to investigate the structure of replicating P22 and lambda phage DNA by physical methods, primarily electron microscopy. Four projects are planned: 1. Determination of the relationship between the origin of phage P22 DNA replication and the unique starting site for DNA encapsulation. The methods combine partial-denaturation mapping with genetic techniques. 2. Does discontinuous synthesis of "Okazaki fragments" occur on one or both strands of each replication fork in replicating lambda DNA? Hybridization to separated lambda strands followed by hybridization to ecoRl fragments of lambda DNA will be used to determine the sites of synthesis of the Okazaki pieces. 3. Development of methods, based on computer techniques, for construction of partial-denaturation maps of large DNA molecules such as bacterial episomes, chromosomes, or a chromosome from yeast. 4. Study of the fine structure of replication forks using proteins of known specificity as markers for structural features such as nicks, gaps, or RNA primers.